However, it is possible to design a pro-soft prodrug, a modified soft drug that requires metabolic activation for conversion to the active soft drug. drug.
Combinatorial Chemistry
Combinatorial chemistry is a technology for creating molecules en masse and testing them rapidly for desirable propertiespropertiescontinues to branch out rapidly. rapidly. Compared with conventional one-moleculeone-moleculeat-a-time discovery strategies, many atresearchers see combinatorial chemistry as a better way to discover new drugs, catalysts, and materials. materials.
The prodrug to drug conversion can occur before absorption, during absorption, after absorption, or at a specific site in the body. body. In the ideal case a prodrug is converted to the drug as soon as the desired goal for designing the prodrug has been achieved. achieved.
nonmetabolizable compounds, characterized either by high lipid solubility and accumulation in adipose tissues and organelles or high water solubility. solubility. They are poor substrates for the metabolizing enzymes; enzymes; the potentially metabolically sensitive parts of these drugs are either sterically hindered or the hydrogen atoms are substituted with halogens to block oxidation. oxidation.
Soft Drug
Soft drugs are biologically active drugs designed to have a predictable and controllable metabolism to nontoxic and inactive products after they have achieved their desired pharmacological effect. effect. The molecule could be deactivated and detoxified shortly after it has exerted its biological effect, the therapeutic index could be increased, providing a safer drug. drug.
Advantages
Elimination of toxic metabolites, thereby increasing the therapeutic index of the drug; drug; Avoidance of pharmacologically active metabolites that can lead to long-term effects; longeffects; Elimination of drug interactions resulting from metabolite inhibition of enzymes; enzymes; Simplification of pharmacokinetic problems caused by multiple active species. species.
Activities used in QSAR include chemical measurements and biological assays. assays. QSAR currently are being applied in many disciplines, with many pertaining to drug design and environmental risk assessment. assessment.
QSAR
Quantitative structure-activity relationships structure(QSAR) represent an attempt to correlate structural or property descriptors of compounds with activities. activities. These physicochemical descriptors, which include parameters to account for hydrophobicity, topology, electronic properties, and steric effects, are determined empirically or, more recently, by computational methods. methods.
Rational Drug Design
Using structural information about drug targets or their natural ligands as a basis for the design of effective drugs. drugs.
Rational drug design is a more focussed approach, which uses information about the structure of a drug receptor or one of its natural ligands to identify or create candidate drugs. drugs. The three-dimensional structure of a protein threecan be determined using methods such as X-ray crystallography or nuclear magnetic resonance spectroscopy. spectroscopy.
The difference between prodrugs and soft durgs
The concepts of prodrugs and soft drugs are opposite, as follow: follow: A prodrugs is an inactive compound that requires a metabolic conversion to the active form; form; A soft drug is pharmacologically active and uses metabolism as a means of promoting excretion. excretion.
Feature
It has a close structural similarity to the lead; lead; It has a metabolically sensitive moiety built into the lead structure; structure; The incorporated metabolically sensitive spot does not affect the overall physicochemical or steric properties of the lead compound; compound;
Molecular Modeling
A technique for the investigation of molecular structures and properties using computational chemistry and graphical visualization techniques in order to provide a plausible three-dimensional representation threeunder a given set of circumstances. circumstances.
Computer simulation of molecular structure, to predict and display shape, calculate minimum energy conformations and dynamic ranges, predict recognition sites, binding orientations, etc. etc.
HighHigh-throughput screens (HTS)
HTS is very rapid and sensitive in vitro screens initially developed about 1989-1991. 1989-1991. HTS now can be carried out robotically on small (submicrogram) amounts of compound (dissolved in submicroliter volumes) are becoming universally used. used. With these ultra-high-throughput screening ultra-highapproaches, it is possible to screen 100,000 100, compounds in a day!